A novel causative factor of injury: Severe burns related to fires and explosions of lithium-ion batteries of electric motorcycles.

Severe burns related to fires and explosions of lithium-ion batteries of electric motorcycles have not been reported to date. We retrospectively studied 419 patients admitted to our burn intensive care unit from January 2016 to December 2021. Of these 419 patients, 26 (22 male, 4 female; median age, 42 years) had burns related to lithium-ion battery fires and explosions, and all of their injury characteristics were similar to those of traditional flame burns. Lithium-ion battery-related burns were the eighth most common cause of burn injuries among all hospitalized patients. The 26 patients comprised 10 unemployed and 16 employed individuals. Twenty-three patients were injured at home during the battery charging process, and three were injured outdoors (one by a fire while the electric motorcycle was stationary and the others two by a fire while riding the motorcycle). The burn sites were distributed over the whole body; the burn area ranged from 10 % to 100 % of the total body surface area, and the burn depth ranged from superficial second-degree burns to third-degree burns. Twenty-three patients had inhalation injuries, and ten underwent prophylactic tracheostomy and intubation. Multiple operations were required for wound repair. Although convenient, lithium-ion electric motorcycles can also cause severe burns. To prevent these injuries, we must increase public safety awareness and education, develop new battery energy storage systems and battery management systems, and ensure the safety of batteries. Consumers should be aware of the potential dangers of lithium-ion batteries and comply with related security measures.

Spatially Confined Engineering Toward Deep Eutectic Electrolyte in Metal-Organic Framework Enabling Solid-State Zinc-Ion Batteries.

Uncontrollable interfacial side reactions generated from common aqueous electrolytes, just like the hydrogen evolution reaction (HER) and dendrite growth, have severely prevented the practical application of zinc-ion batteries (ZIBs). Solid-state ZIBs are considered to be an efficient strategy by adopting high-quality solid-state electrolytes (SSEs). Here, by confining the deep eutectic electrolyte (DEE) into the nanochannels of the metal-organic framework (MOF)-PCN-222, a stable DEE@PCN-222 SSE with internal Zn2+ transport channels was obtained. A distinctive ion-transport network composed of DEE and PCN-222 in the interior of DEE@PCN-222 realizes the efficient Zn2+ conduction, contributing to a high ionic conductivity of 3.13 × 10-4 S cm-1 at room temperature, a low activation energy of 0.12 eV, and a high Zn2+ transference number of 0.76. Furthermore, experimental and theoretical investigations demonstrate that DEE@PCN-222 with its unique channel structure could homogeneously regulate the Zn2+ distribution and effectively alleviate the side reactions. Highly reversible Zn plating/stripping performance of 2476 h can be realized by the SSE. The solid-state ZIBs show a specific capacity of 306 mAh g-1 and display cycling stability of 517 cycles. This unique design concept provides a new perspective in realizing the high-safety and high-performance ZIBs.

Size Dependence of Ultrafast Electron Transfer from Didodecyl Dimethylammonium Bromide-Modified CsPbBr3 Nanocrystals to Electron Acceptors.

Charge transfer efficiencies in all-inorganic lead halide perovskite nanocrystals (NCs) are crucial for applications in photovoltaics and photocatalysis. Herein, CsPbBr3 NCs with different sizes are synthesized by varying the ligand contents of didodecyl dimethylammonium bromide at room temperature. Adding benzoquinone (BQ) molecules leads to a decrease in the PL intensities and PL decay times in NCs. The electron transfer (ET) efficiency (ηET) increases with NC size in complexes of CsPbBr3 NCs and BQ molecules (NC-BQ complexes), when the same concentration of BQ is maintained, as investigated by transient photobleaching and photoluminescence spectroscopies. Controlling the same number of attached BQ acceptor molecules per NC induces the same ηET in NC-BQ complexes even though with different NC sizes. Our findings provide new insights into ultrafast charge transfer behaviors in perovskite NCs, which is important for designing efficient light energy conversion devices.

Epidemiological trends of subarachnoid hemorrhage at global, regional, and national level: a trend analysis study from 1990 to 2021.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke characterized by high mortality and low rates of full recovery. This study aimed to investigate the epidemiological characteristics of SAH between 1990 and 2021. METHODS: Data on SAH incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) were calculated to evaluate changes in the age-standardized rate (ASR) of incidence and mortality, as well as trends in SAH burden. The relationship between disease burden and sociodemographic index (SDI) was also analyzed. RESULTS: In 2021, the incidence of SAH was found to be 37.09% higher than that in 1990; however, the age-standardized incidence rates (ASIRs) showed a decreased [EAPC: -1.52; 95% uncertainty interval (UI) -1.66 to -1.37]. Furthermore, both the number and rates of deaths and DALYs decreased over time. It was observed that females had lower rates compared to males. Among all regions, the high-income Asia Pacific region exhibited the highest ASIR (14.09/100,000; 95% UI 12.30/100,000 - 16.39/100,000) in 2021, with an EPAC for ASIR < 0 indicating decreasing trend over time for SAH ASIR. Oceania recorded the highest age-standardized mortality rates (ASMRs) and age-standardized DALYs rates among all regions in 2021 at values of respectively 8.61 (95% UI 6.03 - 11.95) and 285.62 (95% UI 209.42 - 379.65). The burden associated with SAH primarily affected individuals aged between 50 - 69 years old. Metabolic risks particularly elevated systolic blood pressure were identified as the main risk factors contributing towards increased disease burden associated with SAH when compared against environmental or occupational behavioral risks evaluated within the GBD framework. CONCLUSIONS: The burden of SAH varies by gender, age group, and geographical region. Although the ASRs have shown a decline over time, the burden of SAH remains significant, especially in regions with middle and low-middle SDI levels. High systolic blood pressure stands out as a key risk factor for SAH. More specific supportive measures are necessary to alleviate the global burden of SAH.

Impact of Lymph Node Dissection for Patients With Clinically Node-Negative Intrahepatic Cholangiocarcinoma: A Multicenter Cohort Study.

Background: Lymph node status is a prominent prognostic factor for intrahepatic cholangiocarcinoma (ICC). However, the prognostic value of performing lymph node dissection (LND) in patients with clinical node-negative ICC remains controversial. The aim of this study was to evaluate the clinical value of LND on long-term outcomes in this subgroup of patients. Methods: We retrospectively analyzed patients who underwent radical liver resection for clinically node-negative ICC from three tertiary hepatobiliary centers. The propensity score matching analysis at 1:1 ratio based on clinicopathological data was conducted between patients with and without LND. Recurrence-free survival (RFS) and overall survival (OS) were compared in the matched cohort. Results: Among 303 patients who underwent radical liver resection for ICC, 48 patients with clinically positive nodes were excluded, and a total of 159 clinically node-negative ICC patients were finally eligible for the study, with 102 in the LND group and 57 in the non-LND group. After propensity score matching, two well-balanced groups of 51 patients each were analyzed. No significant difference of median RFS (12.0 vs. 10.0 months, P = 0.37) and median OS (22.0 vs. 26.0 months, P = 0.47) was observed between the LND and non-LND group. Also, LND was not identified as one of the independent risks for survival. Among 51 patients who received LND, 11 patients were with positive lymph nodes (lymph node metastasis (LNM) (+)) and presented significantly worse outcomes than those with LND (-). On the other hand, postoperative adjuvant therapy was the independent risk factor for both RFS (hazard ratio (HR): 0.623, 95% confidence interval (CI): 0.393 - 0.987, P = 0.044) and OS (HR: 0.585, 95% CI: 0.359 - 0.952, P = 0.031). Furthermore, postoperative adjuvant therapy was associated with prolonged survivals of non-LND patients (P = 0.02 for RFS and P = 0.03 for OS). Conclusions: Based on the data, we found that LND did not significantly improve the prognosis of patients with clinically node-negative ICC. Postoperative adjuvant therapy was associated with prolonged survival of ICC patients, especially in non-LND individuals.

Decreased levels of PTCSC3 promote the deterioration of prostate cancer and affect the prognostic outcome of patients through sponge miR-182-5p.

BACKGROUND: Prostate cancer, characterized by its insidious onset and short overall survival, and has seen a rise in incidence over recent decades. This study aims to investigate the expression and molecular mechanism of lncRNA PTCSC3 (PTCSC3) in prostate cancer in order to develop new prognostic and therapeutic biomarkers. METHODS: The level of PTCSC3 in serum and cell samples of prostate cancer was quantitatively measured using RT-qPCR assays. The correlation between the variation in PTCSC3 levels and clinical indicators of patients was evaluated. The survival status of the prostate cancer patients included in the study was evaluated using Kaplan-Meier curve and multivariable Cox analysis. The impact of PTCSC3 overexpression on cell growth and activity was revealed by CCK-8 and Transwell assays. The targeting relationship between PTCSC3 and miR-182-5p was determined by bioinformatics prediction and luciferase activity. RESULTS: PTCSC3 was found to be downregulated in prostate cancer, and its low levels were associated with short overall survival in patients. It influenced the progression of prostate cancer by targeting miR-182-5p. Increasing PTCSC3 levels suppressed the proliferation, migration and invasion levels of cells, and miR-182-5p mimic counteracted PTCSC3's effects on cells. CONCLUSIONS: As a potential prognostic biological factor for prostate cancer, PTCSC3 may regulate the progression of prostate cancer by sponging miR-182-5p and affect the prognosis of patients.

NAT10 inhibition promotes ac4C-dependent ferroptosis to counteract sorafenib resistance in nasopharyngeal carcinoma.

Sorafenib, an anticancer drug, has been shown to induce ferroptosis in cancer cells. However, resistance to sorafenib greatly limits its therapeutic efficacy, and the exact mechanism of resistance is not fully understood. This study investigated the role of N-Acetyltransferase 10 (NAT10) in influencing the anticancer activity of sorafenib in nasopharyngeal carcinoma (NPC) and its molecular mechanism. NAT10 expression was significantly upregulated in NPC. Mechanistically, NAT10 promotes proteins of solute carrier family 7 member 11 (SLC7A11) expression through ac4C acetylation, inhibiting sorafenib-induced ferroptosis in NPC cells. The combined application of sorafenib and the NAT10 inhibitor remodelin significantly inhibits SLC7A11 expression and promotes ferroptosis in NPC cells. In vivo knockout of NAT10 inhibited the growth of sorafenib-resistant NPC. Our findings suggest that NAT10 inhibition might be a promising therapeutic approach to enhance the anticancer activity of sorafenib.

A ratiometric fluorescence sensor for detection of organophosphorus pesticides based on enzyme-regulated multifunctional Fe-based metal-organic framework.

The residues of organophosphorus pesticides (OPs) are increasing environmental pollution and public health concerns. Thus, the development of simple, convenient and sensitive method for detection of OPs is crucial. Herein, a multifunctional Fe-based MOF with fluorescence, catalytic and adsorption, is synthesized by a simple one-pot hydrothermal method. The ratiometric fluorescence sensor for detection of OPs is constructed by using only one multifunctional sensing material. The NH2-MIL-101(Fe) is able catalyze the o-phenylenediamine (OPD) into 2,3-diaminophenazine (DAP) in the presence of H2O2. The generated DAP can significantly quench the intrinsic fluorescence of NH2-MIL-101(Fe) by the fluorescence resonance energy transfer (FRET) and internal filtration effect (IFE), while producing a new measurable fluorescence. Without immobilization or molecular imprinting, pyrophosphate ion (PPi) can inhibit the peroxidase-like activity of the NH2-MIL-101(Fe) by chelating with Fe3+/Fe2+ redox couple. Moreover, PPi can also be hydrolyzed by alkaline phosphatase (ALP), the presence of OPs inhibits the activity of ALP, resulting in the increase of extra PPi preservation and signal changes of ratiometric fluorescence, the interactions of ALP with different OPs are explored by molecular docking, the OPs (e.g., glyphosate) interact with crucial amino acid residues (Asp, Ser, Ala, Lys and Arg) are indicated. The proposed sensor exhibits excellent detection performance for OPs with the detection limit of 18.7 nM, which provides a promising strategy for detection of OPs.

The associations between dysregulation of human blood metabolites and lung cancer risk: evidence from genetic data.

BACKGROUND: Metabolic dysregulation is recognized as a significant hallmark of cancer progression. Although numerous studies have linked specific metabolic pathways to cancer incidence, the causal relationship between blood metabolites and lung cancer risk remains unclear. METHODS: Genomic data from 29,266 lung cancer patients and 56,450 control individuals from the Transdisciplinary Research in Cancer of the Lung and the International Lung Cancer Consortium (TRICL-ILCCO) were utilized, and findings were replicated using additional data from the FinnGen consortium. The analysis focused on the associations between 486 blood metabolites and the susceptibility to overall lung cancer and its three major clinical subtypes. Various Mendelian randomization methods, including inverse-variance weighting, weighted median estimation, and MR-Egger regression, were employed to ensure the robustness of our findings. RESULTS: A total of 19 blood metabolites were identified with significant associations with lung cancer risk. Specifically, oleate (OR per SD = 2.56, 95% CI: 1.51 to 4.36), 1-arachidonoylglyceropholine (OR = 1.79, 95% CI: 1.22 to 2.65), and arachidonate (OR = 1.67, 95% CI: 1.16 to 2.40) were associated with a higher risk of lung cancer. Conversely, 1-linoleoylglycerophosphoethanolamine (OR = 0.57, 95% CI: 0.40 to 0.82), ADpSGEGDFXAEGGGVR, a fibrinogen cleavage peptide (OR = 0.60, 95% CI: 0.47 to 0.77), and isovalerylcarnitine (OR = 0.62, 95% CI: 0.49 to 0.78) were associated with a lower risk of lung cancer. Notably, isoleucine (OR = 9.64, 95% CI: 2.55 to 36.38) was associated with a significantly higher risk of lung squamous cell cancer, while acetyl phosphate (OR = 0.11, 95% CI: 0.01 to 0.89) was associated with a significantly lower risk of small cell lung cancer. CONCLUSION: This study reveals the complex relationships between specific blood metabolites and lung cancer risk, highlighting their potential as biomarkers for lung cancer prevention, screening, and treatment. The findings not only deepen our understanding of the metabolic mechanisms of lung cancer but also provide new insights for future treatment strategies.

The clinicopathologic significance of psammoma bodies in cytology specimens: A series of 78 cases.

BACKGROUND: Currently the clinicopathologic significance of psammoma bodies in cytology specimens are not completely understood, including types of cytology specimens and pathologic conditions frequently associated with this unique cytologic feature. In this study, we undertook a retrospective approach to review the specimen types, cytology preparations, patient characteristics, organs or tissues involved and differential diagnoses in cytology specimens with the finding of psammoma bodies. METHODS: Cytology cases with the finding of psammoma bodies from January 2004 to December 2022 were retrieved from our institution's pathology databases, and their clinicopathological features were reviewed. RESULTS: A total of 78 cytology specimens with the finding of psammoma bodies were recorded in our CoPath system. The mean age at diagnosis was 59 years. The patient group showed female gender predominancy (90%). FNA specimens comprised about 38.5% of total cases. Other common specimen types were body cavity fluids (38.5%), including pleural effusion and peritoneal fluid, and about 20.5% of the cases were pelvic washing performed during gynecologic surgeries. Most cytology cases with psammoma bodies had a malignant diagnosis (69%). About 18% of the cases were in the indeterminate diagnostic categories, with 12% suspicious for malignancy and 6% of the cases with atypical cells. About 5% of cases were placed in the neoplastic category, while 8% of cases were negative for malignancy. About 79% of peritoneal cytology with psammoma bodies were neoplastic and mostly gynecologic tumors. Pleural fluids with psammoma bodies were very likely to be malignant and involved by serous carcinoma (15 of 16 cases, 94%). Papillary thyroid carcinoma was the second most common malignancy in our series, present in about 53% of thyroid cytologies with the finding of psammoma bodies. CONCLUSION: Our study showed that psammoma bodies in cytology preparations were more often associated with malignancies in our study of 78 cytology specimens (69%). The most sampled location in our study was peritoneal cavity, followed by pleural cavity, thyroid, lymph nodes, neck masses, and omentum. The clinicopathologic value of psammoma bodies in predicting malignancy varies depending on locations and specimen types.

Microbiological characteristics of the lower airway in adults with bronchiectasis: a prospective cohort study.

BACKGROUND: Microbial infection and colonization are frequently associated with disease progression and poor clinical outcomes in bronchiectasis. Identification of pathogen spectrum is crucial for precision treatment at exacerbation of bronchiectasis. METHODS: We conducted a prospective cohort study in patients with bronchiectasis exacerbation onset and stable state. Bronchoalveolar lavage fluid (BALF) was collected for conventional microbiological tests (CMTs) and metagenomic Next-Generation Sequencing (mNGS). Bronchiectasis patients were monitored for documenting the time to the next exacerbation during longitudinal follow-up. RESULTS: We recruited 168 eligible participants in the exacerbation cohorts, and 38 bronchiectasis patients at stable state at longitudinal follow-up. 141 bronchiectasis patients at exacerbation onset had definite or probable pathogens via combining CMTs with mNGS reports. We identified that Pseudomonas aeruginosa, non-tuberculous mycobacteria, Haemophilus influenzae, Nocardia spp, and Staphylococcus aureus were the top 5 pathogens with a higher detection rate in our cohorts via combination of CMTs and mNGS analysis. We also observed strong correlations of Pseudomonas aeruginosa, Haemophilus influenzae, non-tuberculous mycobacteria with disease severity, including the disease duration, Bronchiectasis Severity Index, and lung function. Moreover, the adjusted pathogenic index of potential pathogenic microorganism negatively correlated (r = -0.7280, p < 0.001) with the time to the next exacerbation in bronchiectasis. CONCLUSION: We have revealed the pathogenic microbial spectrum in lower airways and the negative correlation of PPM colonization with the time to the next exacerbation in bronchiectasis. These results suggested that pathogens contribute to the progression of bronchiectasis.

Stimuli-responsive mechanically interlocked polymer wrinkles.

Artificial wrinkles, especially those with responsive erasure/regeneration behaviors have gained extensive interest due to their potential in smart applications. However, current wrinkle modulation methods primarily rely on network rearrangement, causing bottlenecks in in situ wrinkle regeneration. Herein, we report a dually cross-linked network wherein [2]rotaxane cross-link can dissipate stress within the wrinkles through its sliding motion without disrupting the network, and quadruple H-bonding cross-link comparatively highlight the advantages of [2]rotaxane modulation. Acid stimulation dissociates quadruple H-bonding and destructs network, swiftly eliminating the wrinkles. However, the regeneration process necessitates network rearrangement, making in situ recovery unfeasible. By contrast, alkaline stimulation disrupts host-guest recognition, and subsequent intramolecular motion of [2]rotaxane dissipate energy to eliminate wrinkles gradually. The always intact network allows for the in situ recovery of surface microstructures. The responsive behaviors of quadruple H-bonding and mechanical bond are orthogonal, and their combination leads to wrinkles with multiple but accurate responsiveness.

Desmoid tumors of rectus abdominis: A case report and literature review.

RATIONALE: Desmoid tumor (DT) is a rare soft tissue tumor that can occur anywhere in the body. Abdominal wall DT presents unique clinical challenges due to its distinctive manifestations, treatment modalities, and the lack of biomarkers for diagnosis and recurrence prediction, making clinical decisions exceedingly complex. PATIENT CONCERNS: A 32-year-old female who underwent radical resection combined with patch reinforcement for rectus abdominis DT, successfully alleviating abdominal discomfort, with no recurrence during the 6-month follow-up after surgery. DIAGNOSES: Based on the imaging studies and medical history, the patient underwent radical surgical resection. Histopathology reveals that the tumor cells predominantly composed of proliferative fibroblasts with local collagen deposition. The lesional cells show positive staining for ß-catenin, indicating a diagnosis of DT. INTERVENTIONS: The patient underwent radical surgical resection with patch reinforcement to repair the abdominal wall defect. Pathology confirmed negative margins, achieving an R0 resection, and genetic testing identified a T41A mutation in CTNNB1. Consequently, no additional adjuvant therapy was administered postoperatively. OUTCOMES: The patient was discharged with the incision healing well after 3 days postoperation. Upon reexamination 6 months later, no recurrence or adverse complications were observed. LESSONS: Abdominal wall DT treatment requires personalized plans from multidisciplinary team discussions. Genetic testing plays a crucial role in identifying novel biomarkers for abdominal wall DT. We have once again demonstrated the significant clinical significance of CTNNB1 mutations in the diagnosis and progression of abdominal wall DT. Additionally, genes such as CCND1, CYP3A4, SLIT1, RRM1, STIM1, ESR2, UGT1A1, among others, may also be closely associated with the progression of abdominal wall DT. Future research should delve deeper into and systematically evaluate the precise impact of these genetic mutations on treatment selection and prognosis for abdominal wall DT, in order to better guide patient management and treatment decisions.

In Vivo-Matured Oocyte Resists Post-Ovulatory Aging through the Hub Genes DDX18 and DNAJC7 in Pigs.

Assisted reproduction technology (ART) procedures are often impacted by post-ovulatory aging (POA), which can lead to reduced fertilization rates and impaired embryo development. This study used RNA sequencing analysis and experimental validation to study the similarities and differences between in vivo- and vitro-matured porcine oocytes before and after POA. Differentially expressed genes (DEGs) between fresh in vivo-matured oocyte (F_vivo) and aged in vivo-matured oocyte (A_vivo) and DEGs between fresh in vitro-matured oocyte (F_vitro) and aged in vitro-matured oocyte (A_vitro) were intersected to explore the co-effects of POA. It was found that "organelles", especially "mitochondria", were significantly enriched Gene Ontology (GO) terms. The expression of genes related to the "electron transport chain" and "cell redox homeostasis" pathways related to mitochondrial function significantly showed low expression patterns in both A_vivo and A_vitro groups. Weighted correlation network analysis was carried out to explore gene expression modules specific to A_vivo. Trait-module association analysis showed that the red modules were most associated with in vivo aging. There are 959 genes in the red module, mainly enriched in "RNA binding", "mRNA metabolic process", etc., as well as in GO terms, and "spliceosome" and "nucleotide excision repair" pathways. DNAJC7, IK, and DDX18 were at the hub of the gene regulatory network. Subsequently, the functions of DDX18 and DNAJC7 were verified by knocking down their expression at the germinal vesicle (GV) and Metaphase II (MII) stages, respectively. Knockdown at the GV stage caused cell cycle disorders and increase the rate of abnormal spindle. Knockdown at the MII stage resulted in the inefficiency of the antioxidant melatonin, increasing the level of intracellular oxidative stress, and in mitochondrial dysfunction. In summary, POA affects the organelle function of oocytes. A_vivo oocytes have some unique gene expression patterns. These genes may be potential anti-aging targets. This study provides a better understanding of the detailed mechanism of POA and potential strategies for improving the success rates of assisted reproductive technologies in pigs and other mammalian species.

Aneuploidy underlies brefeldin A-induced antifungal drug resistance in Cryptococcus neoformans.

Cryptococcus neoformans is at the top of the list of "most wanted" human pathogens. Only three classes of antifungal drugs are available for the treatment of cryptococcosis. Studies on antifungal resistance mechanisms are limited to the investigation of how a particular antifungal drug induces resistance to a particular drug, and the impact of stresses other than antifungals on the development of antifungal resistance and even cross-resistance is largely unexplored. The endoplasmic reticulum (ER) is a ubiquitous subcellular organelle of eukaryotic cells. Brefeldin A (BFA) is a widely used chemical inducer of ER stress. Here, we found that both weak and strong selection by BFA caused aneuploidy formation in C. neoformans, mainly disomy of chromosome 1, chromosome 3, and chromosome 7. Disomy of chromosome 1 conferred cross-resistance to two classes of antifungal drugs: fluconazole and 5-flucytosine, as well as hypersensitivity to amphotericin B. However, drug resistance was unstable, due to the intrinsic instability of aneuploidy. We found overexpression of AFR1 on Chr1 and GEA2 on Chr3 phenocopied BFA resistance conferred by chromosome disomy. Overexpression of AFR1 also caused resistance to fluconazole and hypersensitivity to amphotericin B. Furthermore, a strain with a deletion of AFR1 failed to form chromosome 1 disomy upon BFA treatment. Transcriptome analysis indicated that chromosome 1 disomy simultaneously upregulated AFR1, ERG11, and other efflux and ERG genes. Thus, we posit that BFA has the potential to drive the rapid development of drug resistance and even cross-resistance in C. neoformans, with genome plasticity as the accomplice.

Mechanically Interlocked Polyrotaxane Networks with Collective Motions of Multiple Main-Chain Mechanical Bonds.

Type I main-chain polyrotaxanes (PRs) with multiple wheels threaded onto the axle are widely employed to design slide-ring materials. However, Type II main-chain PRs with axles threading into the macrocycles on the polymer backbones have rarely been studied, although they feature special topological structures and dynamic characteristics. Herein, we report the design and preparation of Type II main-chain PR-based mechanically interlocked networks (PRMINs), based on which the relationship between microscopic motion of mechanical bonds on the PRs and macroscopic mechanical performance of materials has been revealed. The representative PRMIN-2 exhibits a robust feature in tensile tests with high stretchability (1680%) and toughness (47.5 MJ/m3). Moreover, it also has good puncture performance with puncture energy of 22.0 mJ. Detailed rheological measurements and coarse-grained molecular dynamics (CGMD) simulation reveal that the embedded multiple [2]rotaxane mechanical bonds on the PR backbones of PRMINs could undergo a synergistic long-range sliding motion under external force, with the introduction of collective dangling chains into the network. As a result, the synchronized motions of coherent PR chains can be readily activated to accommodate network deformation and efficiently dissipate energy, thereby leading to enhanced mechanical performances of PRMINs.

Neutrophils' dual role in cancer: from tumor progression to immunotherapeutic potential.

The tumor microenvironment (TME) is intricately associated with cancer progression, characterized by dynamic interactions among various cellular and molecular components that significantly impact the carcinogenic process. Notably, neutrophils play a crucial dual role in regulating this complex environment. These cells oscillate between promoting and inhibiting tumor activity, responding to a multitude of cytokines, chemokines, and tumor-derived factors. This response modulates immune reactions and affects the proliferation, metastasis, and angiogenesis of cancer cells. A significant aspect of their influence is their interaction with the endoplasmic reticulum (ER) stress responses in cancer cells, markedly altering tumor immunodynamics by modulating the phenotypic plasticity and functionality of neutrophils. Furthermore, neutrophil extracellular traps (NETs) exert a pivotal influence in the progression of malignancies by enhancing inflammation, metastasis, immune suppression, and thrombosis, thereby exacerbating the disease. In the realm of immunotherapy, checkpoint inhibitors targeting PD-L1/PD-1 and CTLA-4 among others have underscored the significant role of neutrophils in enhancing therapeutic responses. Recent research has highlighted the potential of using neutrophils for targeted drug delivery through nanoparticle systems, which precisely control drug release and significantly enhance antitumor efficacy. This review thoroughly examines the diverse functions of neutrophils in cancer treatment, emphasizing their potential in regulating immune therapy responses and as drug delivery carriers, offering innovative perspectives and profound implications for the development of targeted diagnostic and therapeutic strategies in oncology.

An astroglial basis of major depressive disorder: Molecular, Cellular, and Circuit Features.

Major depressive disorder (MDD) is a common psychiatric disorder and has been a leading cause of disability worldwide. Astrocytes play a role in the maintenance of the function of the central nervous system (CNS), both physiologically and pathologically. Accumulated evidence indicates that the astrocyte is an important contributor to the pathophysiology of MDD including blood-brain barrier (BBB) integrity, gap junctions, gliotransmission, glutamate homeostasis, and energy metabolism. Here, we comprehensively summarize an astroglial basis for MDD based on molecular, cellular, and circuit properties, suggesting that astrocytes appear to be highly sensitive to stress and are likely to be uniquely positioned to integrate peripheral and central stress responses.

Development of potent pan-coronavirus fusion inhibitors with a new design strategy.

Development of potent and broad-spectrum drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains one of the top priorities, especially in the cases of the emergence of mutant viruses and inability of current vaccines to prevent viral transmission. In this study, we have generated a novel membrane fusion-inhibitory lipopeptide IPB29, which is currently under clinical trials; herein, we report its design strategy and preclinical data. First, we surprisingly found that IPB29 with a rigid linker between the peptide sequence and lipid molecule had greatly improved α-helical structure and antiviral activity. Second, IPB29 potently inhibited a large panel of SARS-CoV-2 variants including the previously and currently circulating viruses, such as Omicron XBB.5.1 and EG.5.1. Third, IPB29 could also cross-neutralize the bat- and pangolin-isolated SARS-CoV-2-related CoVs (RatG13, PCoV-GD, and PCoV-GX) and other human CoVs (SARS-CoV, MERS-CoV, HCoV-NL63, and HCoV-229E). Fourth, IPB29 administrated as an inhalation solution (IPB29-IS) in Syrian hamsters exhibited high therapeutic and preventive efficacies against SARS-CoV-2 Delta or Omicron variant. Fifth, the pharmacokinetic profiles and safety pharmacology of IPB29-IS were extensively characterized, providing data to support its evaluation in humans. In conclusion, our studies have demonstrated a novel design strategy for viral fusion inhibitors and offered an ideal drug candidate against SARS-CoV-2 and other coronaviruses.

Structural basis of neuropeptide Y signaling through Y1 and Y2 receptors.

Neuropeptide Y (NPY), a 36-amino-acid peptide, functions as a neurotransmitter in both the central and peripheral nervous systems by activating the NPY receptor subfamily. Notably, NPY analogs display varying selectivity and exert diverse physiological effects through their interactions with this receptor family. [Pro34]-NPY and [Leu31, Pro34]-NPY, mainly acting on Y1R, reportedly increases blood pressure and postsynaptically potentiates the effect of other vasoactive substances above all, while N-terminal cleaved NPY variants in human body primary mediates angiogenesis and neurotransmitter release inhibition through Y2R. However, the recognition mechanisms of Y1R and Y2R with specific agonists remain elusive, thereby hindering subtype receptor-selective drug development. In this study, we report three cryo-electron microscopy (cryo-EM) structures of Gi2-coupled Y1R and Y2R in complexes with NPY, as well as Y1R bound to a selective agonist [Leu31, Pro34]-NPY. Combined with cell-based assays, our study not only reveals the conserved peptide-binding mode of NPY receptors but also identifies an additional sub-pocket that confers ligand selectivity. Moreover, our analysis of Y1R evolutionary dynamics suggests that this sub-pocket has undergone functional adaptive evolution across different species. Collectively, our findings shed light on the molecular underpinnings of neuropeptide recognition and receptor activation, and they present a promising avenue for the design of selective drugs targeting the NPY receptor family.